Hypertension, Vol 9, 178-187, Copyright © 1987 by American Heart Association
GK Owens
The hypothesis that a primary stimulus for aortic medial hypertrophy in
spontaneously hypertensive rats (SHR) is increased blood pressure was
tested by determining whether development of smooth muscle cell hypertrophy
and hyperploidy in SHR could be dissociated from blood pressure levels in
rats treated with various antihypertensive drugs with different mechanisms
of action. Wistar-Kyoto rats (WKY) and SHR were treated between 2 and 5
months of age with captopril (375 mg/L), hydralazine (40 mg/L), or
propranolol (1.5 mg/L) administered in their drinking water. Smooth muscle
hypertrophy and hyperploidy were analyzed by morphometric evaluation of
medial smooth muscle content, flow cytometric analysis of the frequency of
polyploid smooth muscle cells, and biochemical estimates of smooth muscle
cell number. All drugs significantly lowered blood pressure in SHR compared
with untreated controls (order of efficacy: captopril greater than
hydralazine greater than propranolol). Captopril also was most effective at
changing blood pressure in WKY, while propranolol and hydralazine had
similar blood pressure-lowering effects. The efficacy of drugs in
preventing the development of smooth muscle cell polyploidism and medial
hypertrophy in SHR was the same as their efficacy in lowering blood
pressure, although propranolol had no effect on medial smooth muscle
hypertrophy despite lowering blood pressure by 26 mm Hg. Regression
analyses showed a high degree of correlation between blood pressure and the
frequency of polyploid smooth muscle cells and medial smooth muscle
content. These results are consistent with the hypothesis that aortic
medial hypertrophy may be, in part, a response to increased blood pressure
or wall stress. However, analysis of covariance and two-stage multiple
regression analyses indicated that captopril had an effect over and above
that predicted by its blood pressure-lowering effect. Furthermore,
propranolol lowered blood pressure but did not affect medial hypertrophy.
These results suggest that smooth muscle hypertrophy is not simply a
response to increased blood pressure, but that other factors, such as
angiotensin II, may be important in modulating aortic medial hypertrophy in
SHR.
ARTICLES
Influence of blood pressure on development of aortic medial smooth muscle hypertrophy in spontaneously hypertensive rats
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